Infection 5: Pathogenesis of Sepsis

Question 1

Define sepsis

Answer 1

2016 Sepsis 3 criteria “life-threatening organ dysfunction caused by a dysregulated host response to infection”

Question 2

Describe the endotoxin paradigm

Answer 2

Sepsis begins with wide-spread recognition of generic microbial elements (e.g. lipopolysaccharide)
LPS Binding Protein
CD14
Toll Like Receptors
Monocyte / Macrophage
Endothelium
Receptor associated kinases
Regulation of cytokine gene transcription

Question 3

Describe the pathophysiology of sepsis

Answer 3

look at diagram from his slides

Question 4

Describe the CV changes in sepsis

Answer 4

Early distributive shock (warm peripheries)
Peripheral vasodilatation

Then hypovolaemic shock (cold peripheries)
Capillary leak, peripheral and pulmonary oedema
Low filling pressure (fluid responsive)

Late cardiogenic shock (cold peripheries)
Cardiac myocyte suppression
High filling pressure (not fluid responsive)

Question 5

List 3 examples of PAMPs and 3 PRRs

Answer 5

2. Endotoxin is just one example of a Pathogen Associated Molecular Pattern (PAMP)
3. TLR4 is just one example of a Pattern Recognition Receptor (PRR)

Other PAMPS
Lipopeptides
Peptidoglycans
Flagellin
Microbial DNA / RNA

Other PRRs
TLRs1-11
CD14
NOD1 and 2
Beta integrins

Mannose Binding Lectin

Question 6

What is the immunpathogenesis of toxic shock?

Answer 6

Protein exotoxins of certain bacteria
Function immunologically as superantigens

Antigens: trigger T cell responses in tiny proportions of resting T cells
Superantigens: trigger T cell responses in up to 20% of all resting T cells
Superantigen responses are:
Not restricted by antigen specificity of cells
Big

Question 7

sepsis 6

Answer 7

you should know it

Question 8

what is the cut off for the sofa score?

Answer 8

> /= 2 suggests organ dysfucntion